Abstract
In this study, we established a dynamic micromodel of urinary tract infection to analyze the impact of UT-segment-specific urinary outflow on the persistence of E. coli colonization. We found that the adherence of Dr+ E. coli to bladder T24 transitional cells and type IV collagen is maximal at lowest shear stress and is reduced by any increase in flow velocity. The analyzed adherence was effective in the whole spectrum of physiological shear stress and was almost irreversible over the entire range of generated shear force. Once Dr+ E. coli bound to host cells or collagen, they did not detach even in the presence of elevated shear stress or of chloramphenicol, a competitive inhibitor of binding. Investigating the role of epithelial surface architecture, we showed that the presence of budding cells-a model microarchitectural obstacle-promotes colonization of the urinary tract by E. coli. We report a previously undescribed phenomenon of epithelial cell "rolling-shedding" colonization, in which the detached epithelial cells reattach to the underlying cell line through a layer of adherent Dr+ E. coli. This rolling-shedding colonization progressed continuously due to "refilling" induced by the flow-perturbing obstacle. The shear stress of fluid containing free-floating bacteria fueled the rolling, while providing an uninterrupted supply of new bacteria to be trapped by the rolling cell. The progressive rolling allows for transfer of briefly attached bacteria onto the underlying monolayer in a repeating cascading event.
Highlights
We found that the adherence of Dr+ E. coli to bladder T24 transitional cells and type IV collagen is maximal at lowest shear stress and is reduced by any increase in flow velocity
The fimbriae assembled by the chaperoneusher pathway provide strong host-specific adherence which is, strongly modulated by the dynamically changing urine flow in the urinary tract (UT)
Urinary tract infections (UTIs) are among the most common nosocomial and communityacquired bacterial infections affecting up to 150 million people worldwide each year [1]. 65– 85% of UTIs are caused by uropathogenic E. coli strains (UPECs) that reside in the intestine and colonize the periurethral area, ascending stepwise to the bladder, ureters, and kidneys [2,3]
Summary
Urinary tract infections (UTIs) are among the most common nosocomial and communityacquired bacterial infections affecting up to 150 million people worldwide each year [1]. 65– 85% of UTIs are caused by uropathogenic E. coli strains (UPECs) that reside in the intestine and colonize the periurethral area, ascending stepwise to the bladder, ureters, and kidneys [2,3]. The ascending colonization is facilitated by E. coli adhesins that allow pathogens to anchor to specific receptors expressed by uroepithelial lining of the urinary tract, evading elimination by urine flow. The most thoroughly characterized are the cystitis-associated (type 1) and pyelonephritis-associated (P) pili, encoded by the fim or pap operon, respectively. Both are monoadhesins: heteropolymers with a complex subunit composition tipped with a single adhesin molecule, FimH or PapG [7]. Over 90% of UPEC strains produce type 1 pili that mediate mannose-specific adhesion to the bladder epithelium by binding to mannosyl residues via the lectin domain of FimH. Binding of Dr adhesins to DAF, CEACAM receptors and type IV collagen is competitively inhibited by chloramphenicol [15,16,17,18,19]
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